Approximately 470,000 Americans have end-stage renal disease and most are treated with hemodialysis. A vascular access is required for performing the hemodialysis procedure and can be provided with a native arteriovenous (AV) fistula, a synthetic AV graft;or a central venous catheter. The AV fistula is the preferred type of vascular access because thrombosis rates, infection rates, access-related expenditures, and total healthcare expenditures all are lower for patients with fistulas than for those with either synthetic AV grafts or central venous catheters. However, the advantages of fistulas are counterbalanced by the substantially higher proportion of fistulas than grafts that are never able to be used for dialysis because of failure to mature adequately to support effective hemodialysis. Maturation failure is the major barrier to increasing fistula prevalence, and, for many patients, leads to multiple surgical procedures or prolonged use of central venous catheters, the least desirable type of vascularaccess. Recent studies suggest that 20-50% of new fistulas fail to mature. This application is a response to an NIDDK RFA to establish a consortium for designing and performing an observational cohort study of patients with new fistulas. We are applying to be one of the Participating Clinical Centers of the Consortium. The overall objective of this proposal is to identify determinants of fistula maturation outcomes in order to enable early identification of failing fistulas, elucidate mechanisms underlying fistula maturation, and identify potential targets for maturation-enhancing interventions. Our proposal has five specific aims. These include 1) determining the utility of ultrasound as a method for early identification of fistulas that are failing to mature, 2) evaluating the impact of pre-existing vascular function on fistula maturation outcomes, 3) identifying surgical factors that are associated with fistula maturation outcomes, 4) creating evidence-based criteria for fistula maturation, and 5) characterizing the clinical consequences of fistula maturation failure. These aims assume an enrollment of 75-100 subjects over two years at our site for an overall study cohort of 600 subjects. Several of our aims include sub-studies that will be performed in a subset of the subjects to provide additional mechanistic information about the fistula maturation process. Our established research focus and expertise in hemodialysis vascular access, our success and leadership as a Clinical Center for the NIDDK Dialysis Access Consortium (DAC), the multidisciplinary expertise of the collaborators for this proposal, and the resources available at Boston University make us ideally suited to serve as a Participating Clinical Center for this NIDDK initiative.